Their good outcomes may identify them as candidates for therapy reduction2; however, ≈20% of patients experience a relapse, partly with unknown reason, in a subset of initially diagnosed standard-risk patients.3 It is not yet known whether additional secondary genomic alterations in ETV6::RUNX1+ and HD BCP-ALL, particularly the frequently overlooked large-scale structural variations, may help to characterize and subdefine these entities and their outcome even further. This evidence concerns the gene RUNX1 and acute lymphoblastic leukemia.